Process and system for sample analysis

ABSTRACT

Components resolved in time by a separator accumulate in a sample cell and are analyzed by electromagnetic radiation-based spectroscopic techniques. The sample cell can be configured for multiple path absorption and can be heated. The separator can be a gas chromatograph or another suitable device, for example a distillation-based separator. The method and system described herein can include other mechanical elements, controls, procedures for handling background and sample data, protocols for species identification and/or quantification, automation, computer interfaces, algorithms, software or other features.

RELATED APPLICATIONS

This application is a Divisional of U.S. application Ser. No. 14/660,574filed on Mar. 17, 2015, which claims the benefit under 35 USC 119(e) ofU.S. Provisional Application No. 61/954,054, filed on Mar. 17, 2014,both of which are incorporated herein by reference in their entirety.

BACKGROUND OF THE INVENTION

Gas Chromatography (GC) is used to resolve a mixture into its variouscomponents according to retention profiles of the different moleculespassing through the GC column. While the technique can separate mixturescontaining hundreds of substances, identifying the molecules that elutefrom the column is more problematic. To address the need for rapid andsensitive identification of the molecular species present, GC has beenintegrated with techniques such as mass spectrometry (MS) or Fouriertransform infrared (FTIR) spectrometry.

Gas chromatography-mass spectrometry (GC-MS) is probably the mostwidespread tandem technique in the analytical instrumentation industrytoday. GC-MS systems are versatile and are employed across manydifferent industries, particularly for environmental, chemical,petroleum, pharmaceutical, and toxicological applications. While GC-MSis a fast, sensitive technique suitable for multiple component detectionand spectral identification, capable of measuring atomic species andsupported by large available spectral libraries, it suffers from manydisadvantages. These include compound separation to prevent MSinterferences, non-linear calibrations, poor precision and accuracy(requiring constant calibration) and limited dynamic range. Problemsalso are encountered when high concentrations are present that can allowfor chemical ionization to occur, generating questionable data.

To prevent MS spectral overlaps and interferences, the techniquetypically requires fully or nearly fully resolved GC peaks, with limitedto no co-elution. Also GC-MS cannot differentiate between structuralisomers that have identical electron impact and chemical ionization massspectra. Moreover, most GC-MS systems require user selection of a listof compounds prior to analysis (e.g., approximately 60) and then onlyreport those. Although the MS software can then do a global search andtry to identify other peaks, it can seldom perform a quantitativeanalysis. This may be due, at least in part, to the fact that, althoughextensive (10,000s), MS libraries are only qualitative and can differfrom one MS manufacturer to another. Thus unless the MS is calibratedfor a compound, a semi-quantitative analysis remains the best outcomefor a detected peak.

GC-MS systems are also somewhat temperamental. For analysis, GC-MSnormally requires helium or hydrogen gases, which raise cost and/orsafety considerations. Equipment problems can arise with atmosphericleaks due to low operating pressures and, in general, GC-MS systems tendto require frequent maintenance, leading to extensive downtime. Then,bringing the systems back on-line can be time consuming and laborintensive.

While GC-MS is the more commonly deployed solution, GasChromatography-Fourier Transform Infrared Spectrometry (GC-FTIR)provides a powerful analytical tool that is particularly useful todistinguish among structural isomers that have identical electron impactand chemical ionization mass spectra.

SUMMARY OF THE INVENTION

Nevertheless, the designs of existing GC-FTIR systems are also plaguedwith their own limitations. For example, many GC-FTIR couplings utilizea “light pipe” (typically a cell or cuvette used for passing both gaseluted from the GC column, and light from the FTIR interferometer). Thelight pipe is made relatively short to prevent peak dilution through theIR cell and its eventual IR detection or secondary detection. Since IRabsorption is proportional to cell path length, this short path lengthlimits the sensitivity (minimum detection limit (MDL)) of the technique.Problems also arise in cases in which GC peaks come off very quickly.Since the light pipe has a relatively large volume when compared to theflow rates of the GC, the gas can become diluted, making measurementsmore difficult.

A need exists, therefore, for techniques and equipment that addressproblems presented by conventional GC-MS or GC-FTIR techniques andsystems. For example, there is a need for coupling existing or newlydeveloped systems that discriminate or resolve species in time, such asGCs, and/or optical spectroscopy systems, such as FTIRs, in ways thatreduce or minimize the deficiencies encountered with conventional lightpipe arrangements. A need exists as well for simple units and proceduresthat can integrate GCs with other spectroscopic methods suitable foridentifying component species. Also desirable is the integration ofseparation techniques other than GC with FTIR or other spectroscopicanalytical tools.

Generally the invention relates to a system and method that couple atime-resolved separator, in many cases a gas chromatograph (GC), to ananalyzer that relies on optical spectroscopic technology such as FTIR orother spectroscopy technology.

In many of its embodiments the coupling between separator and opticalspectroscopic analyzer is based on a sample cell having particularfeatures. The electromagnetic-based radiation spectroscopic device canbe used to identify and, in many cases, quantify the species present inthe components (peaks) resolved by the separator. Controls, automationinstrumentation, computer interfaces, algorithms and/or software-relatedfeatures also can be provided.

In one aspect, a method for analyzing a sample comprises directingoutput from a temporally-resolved separator to a sample cell, e.g., agas cell that integrates the components provided by the separator.Typically, the sample cell has been partially or fully evacuated.Fluids, e.g., gas(es) are allowed to accumulate in the sample cell,effectively integrating their spectral signatures. Multiple spectraobtained over a time interval can then be averaged to best measure theintegrated concentration in the sample cell. Obtaining a movingbackground that includes spectra from a previously eluted samplecomponent, e.g., previously eluted chemical species, allows for theanalysis of the current eluting components without interference frompreviously eluted components. The integrated and averaged multiplespectra can be corrected by using a similarly collected movingbackground and the corrected data are compared to known spectra toidentify one or more components, e.g., chemical species such as atoms,molecules, molecular fragments, ions, present in the current samplecomponent.

In another aspect, a system for analyzing a sample includes a samplecell coupling a separator that resolves sample components in time and aspectroscopic analyzer, wherein the sample cell is configured forintegrating a sample component generated by the separator and mayaverage the collected spectra during or after each integration iscomplete. In some embodiments, resultant sample data, corrected using abackground that can be a described time before the elution time, areanalyzed for certain compounds expected to elute at that time.

In specific implementations the sample cell is heated. In others it isalso configured for multiple path absorption.

The separator can be a gas chromatograph, a distillation-based separatoror another suitable unit that can temporally resolve or separatecomponents, such as chemical species, present in a sample. While in thecurrent embodiment the separator is a gas chromatography system, inother embodiments separators such as liquid chromatography systems,affinity chromatography systems, supercritical fluid chromatographysystems, ion exchange chromatography systems, distillation systems,fractional distillation systems, thermal desorption systems, pseudodistillation apparatuses, thermogravimetric analysis (TGA) instrumentsor pyrolysis instruments are employed.

In general, according to one aspect, the invention features a sampleanalysis system. This system comprises a separator that providescomponents of a sample over time, a sample cell in which the componentsare integrated, e.g., collected and accumulated, and a spectroscopysystem for obtaining a spectral response of the components in the samplecell.

In different implementations, the spectroscopy system determines thespectral response of the components in the sample cell in one or more ofthe following spectral regions millimeter, microwave, terahertz,infrared (including near-, mid- and/or far-infrared), visible,ultraviolet (UV) (including vacuum ultraviolet (VUV)), x-rays and/orgamma. Further, the spectroscopy system can measure differentcharacteristics, such as absorption spectra, emission (includingblackbody or fluorescence) spectra, elastic scattering and reflectionspectra, impedance (e.g., index of refraction) spectra, and/or inelasticscattering (e.g., Raman and Compton scattering) spectra of thecomponents in the sample cell.

When the separator is a gas chromatography system, it may not require aseparate detection system.

In one embodiment, the spectroscopy system is a Fourier transforminfrared spectrometer.

Preferably, a path length in the sample cell is increased by a multiplepath optical arrangement. A White cell or modified White cell typeoptical arrangement can be used.

Embodiments can include a vacuum pumping device for evacuating orpartially evacuating the sample cell. Further, a valve for isolating thesample cell from a pumping device, a valve for diverting output from theseparator away from the sample cell, a sample cell pressure control, orany combination thereof can be used.

A sample concentrating device, such as a TDT, purge and trap or asolvent concentrating device, can be used for collecting the sample.

In general according to another aspect, the invention features a sampleanalysis method, which comprises providing components of a sample overtime, collecting the components in a sample cell, and obtaining aspectral response of the components in the sample cell.

In general according to another aspect, the invention features a samplecell system. This system comprises a sample cell for integratingcomponents, an input port for receiving components from a separator intothe sample cell, and a spectral analysis path for transporting energythough the sample cell to enable the determination of a spectralresponse of the components in the cell.

Usually, the sample cell is at least partially evacuated.

In general according to another aspect, the invention features a methodfor using a sample cell. This method comprises integrating components inthe sample cell, periodically determining spectral responses of thecomponents in the cell, and using some of the spectral responses asbackgrounds to analyze more recent spectral responses to identify thecomponents.

In general according to another aspect, the invention features a systemfor analyzing a sample. This system comprises a sample cell forintegrating components and analyzing samples, a spectroscopy systemdetermining spectral responses of the components in the sample cell overtime, and a computer system comparing the spectral responses to identifyand/or quantify the components in the sample cell.

In general according to another aspect, the invention features a methodfor analyzing a sample. This method comprises integrating elutedcomponents from the sample in a sample cell, determining spectralresponses of the components in the sample cell over time, and comparingthe spectral responses to identify and/or quantify the components in thesample cell.

In general according to another aspect, the invention features a systemfor analyzing a sample. This system comprises a gas chromatographysystem for eluting components of a sample, a sample cell for collectingand integrating the components, a valve device between the gaschromatography system and the sample cell that is opened for periods torelease slugs of effluent into the sample cell, and a spectroscopysystem determining spectral responses of the components in the samplecell.

Here, the valve device can be a standard valve or a mass flowcontroller, for example.

In general according to another aspect, the invention features a methodfor analyzing a sample. This method comprises eluting components of asample from a separator, collecting and integrating the components in asample cell, periodically releasing effluent from the separator into thesample cell, and determining spectral responses of the components in thesample cell.

In general according to another aspect, the invention features acomputer system for analyzing a sample. This computer system controlsthe generation of components from a sample and their accumulation in asample cell. The computer receives spectral responses of the componentsfrom a spectroscopy system and compares those spectral responses topreviously generated spectral responses to identify and/or quantify thecomponents in the sample cell.

In general according to still another aspect, the invention features amethod for analyzing a sample. This method comprises generatingcomponents from a sample and acquiring spectral responses of thecomponents over time and comparing the spectral responses to previouslygenerated spectral responses to identify and/or quantify newly generatedcomponents.

Practicing the invention can have many advantages. In some of itsaspects, the system and method described herein can be used to detectany optically, such as IR, active vapor or gas. Many spectralresolutions are available depending on the specific application, and thetechnique can measure organics, inorganics, polars, non-polars, acidsand bases on the same system. Low molecular to very high molecularweight compounds can be detected. In comparison to GC-MS, full spectralidentification and quantification are possible, including the capabilityof measuring isotopes or structural isomers. Information about chemicalfunctionalities (e.g., alcohol, ester, ether, ketone, acid, amine,halogen presence, and so forth) present also can be obtained. Typically,the spectra generated are constant, with no cross interaction betweenspecies. Moreover, advantages are realized since a technique such asGC-FTIR can measure or deconvolve many compounds that co-elute. 20+compounds have been demonstrated but more are certainly possible withadvanced analysis algorithms. Significantly, inorganic gases that arenot retained by the GC column can be measured simultaneously and withoutinterference. Overlapping compounds also can be measured becauseinterferences can be removed (blended into the background spectrum) as arun progresses.

Furthermore, low level compounds can be measured in the presence of highconcentration compounds, up to 9 orders of magnitude or even higher. Thetechnique can handle very heavily concentrated samples from directinjection, purge and trap or thermal desorption tubes. In fact, itappears that the system designed herein cannot be saturated with toomuch sample.

Conventionally, high volume injection ports are used with detectorscapable of handling larger sample sizes such as flame ionizationdetector (FID), thermal conductivity detector (TCD), electron capturedetector (ECD), electrolytic conductivity detector (ELCD) ornitrogen-phosphorus detector (NPD). These, however, cannot providequalitative spectra. On the other hand, MS detection is not typicallyused in conjunction with high volume injections arrangements, since itrequires splitting the sample to reduce loading. In contrast, largesolvent peaks will not necessarily damage the system described herein,since there is no filament or detector in contact with the gases todamage or potentially burn out. As a result, there is no need to splitthe sample injected into a GC separator and relatively large injectionvolumes are possible. Loss of peak resolution due to larger samples isalso a non-factor since each peak will be integrated over time. Problemsassociated with chemical ionization and other ion interactions at higherconcentrations are also eliminated.

Whereas existing approaches measure peak signal, embodiments of thesystem and method described herein provide an integration of the peaksignal, enhancing signal-to-noise ratios (SNR) over existing technology.As further described below, some spectra can be chosen for backgroundand others for compound measurements as a gas enters and fills a samplecell, resulting in integral effects compared to conventional approaches.Significant SNR advantages also are realized when all of a component gasis monitored at the end of its elution peak.

Since the sample is integrated, the chromatography does not present asimportant an issue and approaches disclosed herein can allow for broaderGC peaks without loss in detection limit, yielding the same resultsregardless of the chromatography. Comparing the same sample separated ina short column with one separated in a long column yielded basically thesame results. Thus the integrating nature of the present techniques andsystem allows having one calibration that could be used on anyseparation device.

In many cases, full resolution of peaks generated by the separator isnot required. Moreover, this makes possible utilizing separators thatresolve mixture components to a lesser extent than is morecharacteristic of most GC-MS systems (e.g., shorter columns, largerdiameter columns, packed columns and so forth could be incorporated).One implementation described herein includes a “pseudo distillation”separator capable of working with very large samples. In turn, this canresult in very low MDLs (e.g., <1 pg/μl in the original sample).

Systems and techniques described herein can reach MDLs that are at,near, or below corresponding GC-MS systems without the MS detectordrawbacks. For instance, low MDLs are expected with samples collected onThermal Desorption Tubes (TDT), solvent concentrates, or purge and trapsystems. MDLs can be automatically determined for each compound in alibrary during each sample analysis. For instance, air samples can becollected onto a TDT, e.g., at a flow rate of 100 mL/minute, for longperiods of times, e.g., hours, or even days depending on the materialbeing trapped, allowing for % to ppt (parts per trillion) or lowerdetection limits for compounds found in the ambient air. Samplecollection is easy, inexpensive and contains no complicated mechanicalparts for opening or closing the tube. In many aspects, flows can beset, preset and/or, maintained at a constant rate and samples can becollected without operator oversight over a predefined time frame.

The GC-FTIR technique and system disclosed herein can, in many cases,outperform GC-MS, if such performance is required. Unlike in MS-basedapproaches, optical or IR spectral calibrations can be constant for thelife of the instrument or type of spectrometer. Once established, e.g.,by operator or instrument supplier, the need for recalibration isexpected to be low or non-existent. Due to the IR absorption spectrumfor each component remaining constant or near constant for mostcompounds at a constant temperature. A change in pressure can affectsome very light molecules absorption profile but additional data couldbe added to the library to make corrections for any pressure change.Component integration in the gas cell further reduces any calibrationvariability from changes in the chromatography or separation. Thus aspectral library can be constructed that is constant in qualitative andquantitative nature and can be transferred between like instruments withwidely ranging separation systems.

Whereas MS libraries are primarily qualitative, spectral libraries used,e.g., in FTIR analysis if collected correctly, are fully quantitative.Unlike GC-MS, the approach described herein also allows monitoring forevery compound in a library as the chromatography, separation ordistillation progresses.

Many spectral calibrations can be very linear throughout entire analysisranges and no further calibration may be required after initial thecalibration by manufacturer or customer. Percent to parts per trillionor less measurements can be obtained with the same configuration with nomodifications.

Generally, the system described herein is rugged, requires limitedservice, with quick starts and restarts. It can be used in the fieldwithout concerns regarding instrument damage or long warm-up periods.Advantageously, the chromatography can run on N₂. Pressures can be fromnear zero up to and potentially exceeding atmospheric. Some embodimentsdisclosed herein do not require helium, hydrogen, turbo pumps, electronionization (EI) sources, or secondary GC detection devices, simplifyinginstrument operation and maintenance requirements. In many of itsimplementations, the invention allows any GC supplier or user to couplean existing GC to any commercial FTIR or other spectroscopic instrument.

Other advantages relate to the moving background described herein, sinceany change in the spectrometer response, possible especially during along run, is removed. Without this feature, a baseline change that is inany way not a linear change affects the detection of low level compoundssince the peak would be less than the compound peak size. Thus lateeluters would be compared to a background that is moving around andchanging and since late eluters are diffusing in the sample (gas) cell,the peak will be drawn out, giving the appearance of a baseline shift atlong times. These two issues are addressed by the integration andbackground shifting disclosed herein.

The above and other features of the invention including various detailsof construction and combinations of parts, and other advantages, willnow be more particularly described with reference to the accompanyingdrawings and pointed out in the claims. It will be understood that theparticular method and device embodying the invention are shown by way ofillustration and not as a limitation of the invention. The principlesand features of this invention may be employed in various and numerousembodiments without departing from the scope of the invention.

BRIEF DESCRIPTION OF THE DRAWINGS

In the accompanying drawings, reference characters refer to the sameparts throughout the different views. The drawings are not necessarilyto scale; emphasis has instead been placed upon illustrating theprinciples of the invention. Of the drawings:

FIG. 1 is a schematic diagram of a conventional GC-FTIR system that usesa “light pipe” optical gas cell.

FIGS. 2A and 2B are schematic diagrams of a sample analysis system(e.g., GC-FTIR) system according to embodiments of the invention.

FIG. 3 is an illustrative schematic diagram of a White cell arrangement.

FIG. 4A is a flow diagram illustrating the control of the system 10 bythe computer system 34 and determination of component absorbancespectra.

FIG. 4B is a flow diagram illustrating the control of the system 10 bythe computer system 34 and determination of component absorbance spectraaccording to another embodiment.

FIG. 4C is a schematic plot of concentration over time showing howbackground and current spectra are determined according to anotherimplementation.

FIG. 4D is a flow diagram illustrating the analysis of the samplespectra to determine component concentrations.

FIG. 5 is a schematic diagram of a distillation-based separator.

FIG. 6 is a schematic diagram of a high volume injection assembly.

FIGS. 7-11 are plots obtained by practicing aspects of the invention.

FIGS. 12A and 12B are screen shots of a user interface generated by thecomputer system 34, in which FIG. 12A includes a top graph 1210 showingis a pseudo chromatogram of peak signal verses time and a bottom graph1212 showing a spectrum related to the point 1214 in time, and FIG. 12Bshows a reporting method having mass (ng) or concentration on the y-axisand compounds shown as a single line (bar graph) at their respectiveR.I. (Retention Index).

DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

Many existing arrangements that involve a GC and FTIR analyzer couplethe two via a light pipe optical gas cell. Shown in FIG. 1, for example,is system 11 including GC and FTIR sections.

During operation, a sample is injected at injection port 13 of the GCsection, and directed through GC column 15, typically heated by oven 17.Output from the column enters light pipe 19 (often heated by an oven,not shown in FIG. 1 near end 21), exits the light pipe near end 23 andis sometimes directed to a secondary GC detector 25, usually a flameionization detector (GC-FID) or thermal conductivity detector (TCD). AFID detector relies on a hydrogen/air flame to oxidize organic moleculesand produce electrically charged particles (or ions). A TCD relies onthe difference of thermal conductivity between the carrier and sampleanalyte gas to sense eluting components.

In the FTIR section of arrangement 11, IR generated by source 27 andmodified according to the principles of Fourier transform spectrometry,using device 29, typically a Michelson interferometer, is directed toend 21 of light pipe 19 and exits the light pipe at end 23, both endsbeing provided with IR transparent windows.

From the light pipe, output radiation is directed to IR detector 31,usually a mercury cadmium telluride (MCT) detector. Signals generatedand data are typically handled by electronics 33 and processingequipment 35.

The present invention generally relates to techniques and equipment foranalyzing a sample, typically a mixture containing more than onedistinct chemical species. Components in the sample can be separatedthrough techniques such as gas chromatography or another suitableseparation method, for example a distillation or distillation-likeprocess or other process that resolves the different chemical species intime. Chemical identification of the species present in the sample iscarried out by optical spectroscopy, such as, for instance, FTIR.Coupling between separator and analyzer is through a sample cell havingone or more features further described below.

Shown in FIGS. 2A and 2B, for example, is system 10, including aseparator such as gas chromatograph (GC) 12, sample cell 14, forinstance a multiple pass cell such as a White cell or modified Whitecell with aspherical optics, further described below, and aspectrometer, e.g., FTIR spectrometer 16, which includes a light, moregenerally EM radiation, source. In specific implementations, GC 12and/or FTIR spectrometer 16 are commercially available instruments, withexhaust from the GC being often directly coupled to the FTIR samplecell.

In general, the GC uses a stationary phase, which is typically amicroscopic layer of liquid or polymer on an inert solid glass or metaltube, i.e., a column. The mobile phase is a carrier gas, usually aninert gas such as helium or an unreactive gas such as nitrogen. Thecarrier gas flow is controlled by flow controllers and/or a series ofvalves to maintain or vary the flow rate during the separation. The flowcontrollers and valves can also be utilized to allow the entire sampleor a fraction of the sample to enter the column. The column is locatedin an oven where the temperature of the gas passing through the columncan be controlled. The gaseous compounds interact with the walls of thecolumn or stationary phase, causing each compound to elute at adifferent time, known as the retention time of the compound.

In other embodiments, instead of a GC separator, another type ofseparator is used such as a liquid chromatography system, affinitychromatography system, supercritical fluid chromatography system, ionexchange chromatography system, distillation system, fractionaldistillation system, thermal desorption system, thermogravimetricanalyzer, pyrolysis instrument, or pseudo distillation apparatus.

In the example of a GC separator 12, it can be operated with or withouttypical GC detection, e.g., with or without the FID/TCD/MSD (massspectrometer detector) arrangement mentioned above. Examples of GCcolumns that can be used include but are not limited to current smallbore (e.g. 0.20-0.75 mm outer diameter (OD)) capillary columns,traditional packed columns (⅛ inch; ¼ inch OD), short packed ¼ inch ODglass or stainless steel (SS) columns, wide or mega-bore (mm OD)columns, packed or mega-bore (mm OD) coated columns and so forth.

The sample can be introduced to GC 12 via an injection arrangement suchas a direct injection port, or static or flow-through sample loops. Inmany cases the subsequent sample injection requires no sample split andcan be, for example, on column or split-less. In some embodiments, theinjection arrangement incorporates elements suitable for concentratingthe sample. Examples include but are not limited to thermal desorptiontubes (TDTs), purge and trap systems (using cold or cryo traps), solventconcentration arrangements and so forth. Sample volumes can be thestandard direct injection volumes of about 1 microliter (μL) used inconventional GC-MS equipment or significantly larger injection volumes(eg. 100+ μL). In many embodiments, and in particular in conjunctionwith larger GC columns or a separator such as the pseudo distillationseparator further described below, system 10 can handle considerablylarger direct injection samples, e.g., from about 100 μL to about 1 mL.

Some approaches can utilize Programmed Temperature Vaporizing (PTV orPVT), a widely used technique to slowly vaporize large samples so thatthe solvent is boiled off and typically diverted from the GC column,leaving the higher boiling material to condense near or at the beginningof the column. In one example the injection system is a MultiMode Inletsystem produced by OPTIC. The current version (OPTIC-4), for instancecan be used for hot injections, cold injections, large volume, on-columninjections, in liner derivatisation, thermal desorption, pyrolysis andso forth. The design of the injector body of this type of injectionsystem is described, for example, in U.S. Pat. No. 8,180,203, with thetitle Direct Heating Tube and Method of Heating Fluid Using Same, issuedto Kurano on May 15, 2012, the contents of which are incorporated hereinby reference.

Some embodiments disclosed herein employ a guard column or a retentiongap column, to prevent, for example, possible damage to the columncoating caused by solvents or to facilitate their removal from thecolumn. Generally, both types of column utilize deactivated fused silicatubing, without a stationary phase, to minimize solute interactions.This tubing can be attached to the front of the column through asuitable union connection.

Typically, guard columns are selected for samples containingnon-volatile residues that may contaminate a column, resulting in thenon-volatile residues being deposited in the guard column and not in thecolumn. This reduces the interaction between the residues and the samplesince the guard column does not retain the solutes (since it contains nostationary phase). Also, Guard columns prevent coating of the stationaryphase with residues, mitigating poor peak shapes.

Retention gap columns are used to improve peak shapes in cases such aslarge volume injections (>2 μL) and solvent-stationary phase polaritymismatch situations in split-less, Megabore direct and on-columninjections. Typically, a retention gap column allows liquid or highconcentration solvent vapor to move into the column without retention sothat the compounds of interest can focus on the head of the GC column.In some cases, benefits of a retention gap are seen when using a guardcolumn.

Specific implementations illustrate advantages over conventionaltechniques that utilize TDTs. Normally, thermal desorption devicesdesorb to a secondary trap to further concentrate the sample, with afairly high flow (10 s of mL/min). During that time the sample is manytimes split. The secondary trap is then desorbed and sent to the GCwhere it is split again. At 10 s of mL/min, the GC will only accept 1 or2 mL/min. Thus each time a TDT or focusing trap is used, sample is lostdue to splitting or just passing through the material (unretained). Thisis done to make sure the peaks are as narrow as possible, so that a MScan analyze them.

However, the equipment and techniques described herein do not requirenarrow peaks (since the separation is in the spectral domain and notevery molecule is needed), it was found that the TDT can just desorbdirectly to the GC without focusing and at low flow rates that work withthe GC, for instance at 2 mL/min. It was also found that thermaldesorption can take place at higher flow rates up to what the column canphysically flow when working with semi-volatile organic compounds(SVOCs). While the light material is desorbed and passes through thesystem, the SVOCs are trapped at the head of the column or Retention gapcolumn until the GC is heated. So the Column acts as the focusingdevice. Once everything is off the TDT, the flow rate is turned down tonormal GC flow rates and the heating of the column is initiated to getthe SVOCs off.

In some implementations, the injection port is designed to boil off thesolvent or injection gas but condense the rest of the sample within theinjection port. This ensures that the only materials passing through GC12 are the compounds of interest and would be particularly useful whenanalyzing semi-volatile, near non-volatile species or samples where thesolvent is significantly more volatile than the sample and potentiallyat significantly higher concentrations.

In a design suitable for running extremely large samples, asplit/splitless injection port can be modified so that the split is a100% to the exhaust side until the solvent is exhausted but the lessvolatile materials are still residing within the injection port. At thispoint, the mode is switched 100, to the column. See, for example, theinjection assembly 80 of FIG. 6, further described below. Known PTV orPVT techniques also can be employed.

Carrier gases that can be employed include nitrogen (N₂), for instanceultra high purity (UHP) N₂, or another suitable gas or gas mixture,e.g., as known in the art.

Typically output from the separator, e.g., GC 12, is in a gaseous state,containing one or more gases and/or vapors. This output is directed tosample (also referred to herein as gas) cell 14, typically a vessel thatcan be evacuated and configured to maintain a gas pressure lower thanthe surrounding (atmospheric or ambient) pressure. In specificimplementations, the pressure in the sample cell is within the range ofabout 0.001 to about 1.0 atm. For instance, a flow rate of 1 mL/minute,a sample cell volume of 200 mL and a starting gas cell pressure of ½atmosphere can provide a 100 minute time period for data acquisition.This is considered to be a sufficient time window for most GC sampleanalyses. In one example, a flow rate of about 1.5 mL/min was found toprovide an optimum resolution in the case of a 0.53 mm OD column withN₂. It was also found that switching to lower pressures may help clearthe cell much faster between runs. In illustrative situations, thepressure is lowered to a value within the range of from about 0.1 toabout 0.01 atm.

In specific examples, sample cell 14 is heated with a heater 36. Thisfeature is particularly useful when analyzing gases with varying vaporpressures or boiling points, e.g., when measuring semi-volatile or evennearly non-volatile compounds. In examples, the heater 36 for heatingsample cell 14 includes but is not limited to heating tape, heatingjackets, ovens, Peltier heaters/coolers, cartridge, immersion, and soforth. A survey of many compounds, including compounds that boil attemperatures above 300° C. showed no condensation with a gas cell at191° C. or 375F. IR optics and spectrometers work better at lowertemperatures. Lightpipes are routinely kept at 300° C., due (at least inpart) to the higher concentrations found in the lightpipe.

The pressure in the sample cell is reduced with the help of vacuum pump18, e.g., a traditional foreline oil pump, a diaphragm pump or anothersuitable pump or alternative apparatus capable of drawing a vacuum. Thepressure in the sample cell can be monitored with a sensor, such as, forinstance, absolute pressure sensor 20.

In some cases, no vacuum is required and the system can be operated at asuitable pressure. For instance, a compressor or column head pressurecould be used to compress the output from the GC into the sample cell14. Preferably, over pressurizing is avoided.

Sample cell 14 also receives electromagnetic radiation, for instancefrom light generated in FTIR arrangement 16 and can be designed to fitin the sample compartment of a commercial FTIR or other type ofspectrometer. The cell is provided with optical components, such as, forexample, windows, that allow transmission of an electromagneticradiation beam within a desired wavelength (or frequency) range.Examples of suitable materials that can transmit IR include potassiumbromide (KBr), potassium chloride (KCl), cesium iodide (CsI), bariumfluoride (BaF₂), sodium chloride (NaCl), calcium fluoride (CaF₂),magnesium fluoride (MgF₂), zinc selenide (ZnSe), zinc sulfide (ZnS),thallium bromoiodide (KRS-5), silver chloride (AgCl), silver bromide(AgBr), lithium fluoride (LiF), sapphire, diamond, silicon, germanium,fused silica, AMTIR-1 (Ge₃₃AS₁₂Se₅₅) and various silicon, cadmium,selenium and germanium based glasses and many others, as known in theart.

Sample cell 14 can be configured for multiple-path (also known asmultiple-pass or long path) absorption. As seen, for instance, in FIG.2B, reflector 30A directs the electromagnetic beam from a source, e.g.,FTIR arrangement 16, to sample cell 14, configured for multiple passabsorption, indicated by the arrows. By increasing the path lengthtraveled, multiple-pass arrangements can be used to measure lowconcentration components or to observe weak absorption spectral featureswithout increasing the physical length or volume of the cell itself.Since the detection limit of the system is directly related to thevolume/path length ratio, decreasing the volume or increasing the pathlength lowers the concentrations that can be detected. Assuming nosignal losses, doubling the path length or reducing the volume in halfwill lower the MDL by a factor of 2.

Normally, multi pass cells do not utilize extreme reflections due tolosses not from the mirrors or their coatings but because ofcontamination from the sample. A gas emerging from a GC, however, isfairly clean and relatively free from particulate matter. In addition oralternatively, contaminants can be controlled in cells configured to besealed or nearly sealed, and never opened. While any suitable materialcan be utilized to form the cell seals, metal seals provide the addedadvantage of circumventing small atmospheric leaks or “virtual” leaks orbleed from the O-ring materials. Based on the low level of contaminationencountered in the embodiments described herein, the cell can bedesigned with significantly more passes through a similar volume andbase path length. The optical throughput of the cell can then becalculated by the reflectivity to the order of passes (i.e.,0.995^128)=0.526 or nearly 53% transmission). In comparison, a gas cellat 32 passes and 0.985 reflectivity is about 0.6 (60% transmission) or 4times less sensitive.

In some cases, existing light pipe technology quotes 5 ng detection forvery strong absorbers. While having a concentrated sample into theanalyzer is advantageous, conventional cells suffer from typically shortpath lengths and losses in the light reaching the detector. Designs suchas described herein can result in 10 to 25 times better SNR once thesample cell path length to volume ratio is optimized.

In certain embodiments, longer path lengths are used in combination withhigher reflective coatings like enhanced silver, yielding a reflectivityin the 0.992 to 0.995 range or greater. Coating optimizations, in the IRregion, for example, could further improve reflectivity, e.g., by afactor or 4 to 8 or even more.

Thus several factors can be important in optimizing the sample celldesign. Considering the path length to volume ratio, many FTIR gasanalyzers with a 5 meter (m) path have a volume that is 10 times larger,making the peaks 10 times smaller. The ultimate sensitivity will beachieved when the longest path length possible is attained, whilemaintaining the gas cell at 200 mL or smaller. This will be based onreflectivity and aberrations due to cutting the mirror surface. 128 to256 passes should be possible with known coatings. 1,000 passes might bepossible based on Cavity Ring-Down techniques and laser technology wherereflectivity can be 0.999 or greater, which can be implemented in otherembodiments. Compared to a sample (gas) cell having 32 passes andproviding 5 m (such as one of the sample cells used to demonstrateaspects of the invention), a gas cell with 128 passes would produceabsorptions 4 times higher. With a high reflectivity mirror coatingthere would be no significant loss in throughput. At a theoretical0.999, 1000 passes could be used, with only a 50% loss in signal. Thatwould generate 31 times the absorption of the 5 m cell and 15.5× lowerMDL.

In specific implementations, sample cell 14 can be configured as a“White cell” type. The principles of a traditional White cellarrangement, employing three spherical concave mirrors having the sameradius of curvature, are illustrated in FIG. 3. Shown in this figure isWhite cell 39, including light source 41 and concave reflectors 43, 45and 47. As seen in this schematic diagram, a light beam generated by thelight source or a spectrometer, photometer or interferometer isreflected between reflector 43 and reflectors 45 and 47, exits theoptical configuration defined by the three reflectors and is directed todetector 22. While the position of the input and output beams remainsunchanged, the number of traversals can be varied by slight rotations toeither element 45 or 47. Generally, the total number of traversals in aWhite cell is a multiple of 4.

Second generation multiple-path gas cells can use non-spherical concavemirrors to improve image quality and optical throughput. Some secondgeneration designs have mirrors (such as mirrors 45 and 47) cut onto asingle metal or glass blank (see, e.g., FIG. 2B, element 14). Thisprovides a fixed path length and the mirrors can be the solid end capsof the gas cell allowing for smaller sample cells that are easier toalign.

In specific examples, the modified White cell employed in system 10 is afixed path cell, with no adjustment for path length. Such a designreduces the number of variables to be monitored and/or controlled. Inone instance, the White type cell has a volume of ˜200 mL. Using goldmirrors can produce a path length of about 5.11 meters (m), whileenhanced silver mirrors can result in a path lengths of 10 m or muchlonger. This increase in path length and change from gold to silverimproves the throughput of the gas cell and provides an approximatedoubling or more of the absorption signal which further reduces theanalyte MDLs.

In many implementations, the White cell utilized, e.g., a secondgeneration White cell, is heated, for example to a temperature such as150° C., 200° C., 250° C., 300° C. or higher, facilitating the use ofthe gas cell to analyze samples with varying vapor pressures or boilingpoints, e.g., to measure semi-volatile or even nearly non-volatilecompounds. As described above, suitable heating means include but arenot limited to heating tape, heating jackets, ovens, Peltier heaters,cartridge heaters, immersion heaters, and so forth.

Other multiple pass cell designs can be utilized. Examples include butare not limited to Herriott cells, Pfund cells, cavity-ring down cells,and integrating spheres.

Referring back to FIGS. 2A and 2B, output radiation exits sample cell 14and is directed by reflector 32 to detector 22, for instance a MCTdevice suitable for measuring the light in an FTIR. Specific examplesemploy liquid nitrogen (LN₂) cooled MCTs. A suitable detector for abroad spectral analysis capability can be a 1 mm mid-band MCT with acutoff of 16 μm. 0.25 mm to 0.5 mm mid band detectors, 22 to 16 μmdetector cutoffs also can be used, typically for broad analysis, while 7to 5 μm detector cutoffs can be selected for more specialized analysesto even lower MDLs. Numerous other detectors could be utilized but notlimited to, such as InSb, InSb/MCT two color detectors, silicon, InGaAs,AlInGaAs, PbS, PbSe, Ge, TGS, DTGS, LiTaO₃. Different coolingtechnologies can be utilized for the detectors such as TE (Peltier),Stirling, LN₂, and liquid He.

A very narrow band MCT detector can be employed in some situations,offering about an order of magnitude improvements in sensitivity.Currently, very narrow band MCT detectors are only operational in the1-5 μm range. This range covers the C—H and O—H stretching region. Whilehydrocarbon identification is typically based on the 5-20 μm fingerprintregion, there appears to be enough variation along with GC separation tomake feasible hydrocarbon specification using the 1-5 μm range, at leastfor some applications. As an added advantage, very narrow band MCTdetectors can run thermoelectrically- or TE-cooled as compared to LN₂cooled.

LN₂ is not always required with other types of detectors, e.g., if DTGS(deuterated triglycine sulfate) detectors are employed, for continuousoperation, for example.

The system can be provided with one or more valves. For the IR exhaustinterface, for example, one or more valves 24 can be disposed betweenpump 18 and the exhaust of sample cell 14. The valve system can fullyopen the sample cell to the vacuum pump or can open and close tomoderate the sample cell pressure to a desired level. Fluid flow out ofthe sample cell can be monitored and/or adjusted, for example with amass flow controller.

One or more additional valves can be included at the GC-FTIR interface.For example, system 10 can include a heated two directional valve, shownin FIG. 2B as elements 26A and 26B, one direction going to the IR andthe other to a bypass to a vacuum pump. In specific examples, both thesample cell and bypass are held at the same low pump pressure. Includingsuch a directional valve could allow for solvent or injection rejectionas it elutes from the separation device, the possibility for very largesample injections, mega-bore columns or large packed columns (whilestill making possible low parts per trillion (ppt) detection levels),removal of volatile organic compounds (VOCs) from semi volatile organiccompounds (SVOCs) analyses, and so forth.

In another possible operating mode, directional valve 26 a is opened forshort periods by the computer system 34 to release a slug of effluentfrom the GC to the gas cell and then closed again, thus maintaining aconstant concentration in each run. It also can give a constantbackground for comparison purposes. This approach can reduce the size ofthe data set since the only spectra gathered are collected after a slugof gases are added. In this mode, a 60 minute run could translate into60 points or 120 points or some other number. Valve 26 a can be designedand/or optimized to prevent leakage when heated. In one implementation,the directional valve 26 a is implemented as a mass flow controller thatcontrols the flow of effluent from the separator 12 e.g., GC 12, intothe gas cell 14.

System 10 can include electronics, computer systems, video displays,devices, units, interfaces and/or other components for data processing,analysis (including multivariate qualitative and quantitative),recording, reporting, equipment controls, automation, flow control andcontrollers, pressure sensors and controllers, heaters and temperaturecontrollers, valves and vacuum generation technology, spectrallibraries, and so forth. These components are generated indicated byreference 34.

During operation, gas is captured in sample cell 14 for a specific time,based on the gas turnover rate in the sample cell. Various flowconditions can be employed. In a transient mode, for instance, theentire experiment (run) is conducted under a set, i.e., unchangingpressure, e.g., under a set vacuum pressure. In a full integration mode,sample cell 14 is evacuated and the sample is allowed to accumulate inthe sample cell, with the pressure changing throughout the analysis.Also possible is a partial integration mode, where the sample cell isevacuated to a set pressure and a dilution gas is added and maintainedin the cell for a period of time, e.g., 1 minute. Other operating modescan be employed, such as, for example, a mode that reduces the size ofthe data set, as described above.

In some arrangements, a continuous carrier gas flow of N₂ (or othercarrier gas) is directed from GC 12, into the sample cell. If desired,sample cell 14 can be closed to the N₂ flow from GC 12, for a given timeinterval. In yet other arrangements, the carrier gas, e.g., N₂, or thesample from the GC can be diverted to a secondary pumping service (notshown in FIG. 2B) to prevent spectral interference from largeconcentration compounds such as solvent species. The flow can then beswitched for sample collection. If pumping continues, the compounds thatcome off during this time will be standard chromatographic components(peaks) and their concentrations can be calculated as such. The peakwill go up and go down as it enters and exits the sample cell so nofurther averaging will be done.

If sample cell 14 is initially evacuated, then sealed from pump 18, thecarrier gas and sample components from the GC can accumulate in thesample cell and spectra can be obtained during the entire datacollection. Since the chemicals are captured in the sample cell, theentire amount of each gas (compound) can be measured once it hascompletely eluted from the separation device (GC). Since the gas cell isa multiple pass gas cell in a preferred embodiment, there can be anincreased absorption for each gas when compared to “light pipe” systemin an optimized design. By letting all the gas remain in the gas cell,this in effect integrates the sample peak from a traditional analyzerwhere the sample moves past or through the detection system. Thisintegration provides a further enhancement in SNR, which can be a factorof 2 to 5 times since the entire amount of sample is measured once ithas completely eluted. Typically, this improvement is dependent on thewidth of the eluted peak. Narrow peaks will have less of an enhancementthan late eluting compounds that may be a minute in length or longer.But this is another advantage of this technology since sensitivity isnot lost by having late eluting compounds that spread out in time. Also,since the analysis is looking at the integration of the peak, manysubsequent spectra can be co-added to further reduce the noise level andimprove the detection limits. Increasing from 1 sec of data collectionto 60 sec can improve the SNR by nearly a factor of 8. So, theaforementioned enhancements may improve the SNR or MDLs relative to someof the current “light pipe” designs.

To improve the analysis/analyzer specificity, the background spectrumwill change with time. Initial background spectra will be acquired priorto sample elution then as time goes on; the background spectrum will becreated from previous sample spectra (average of sample spectra)collected prior to the current sample spectra and compound elution. Bymoving the background spectrum in time, all compounds in the gas cellprior to the current background no longer will exhibit spectral featuresin the absorbance spectrum. The closer in time between this dynamicbackground and the current spectra, the more reduced the chance that anypreviously eluted compounds will affect the current measurement. Thismoving background will allow for the measurement of trace compounds inthe presence of very high concentrations as long as the compounds areseparated in time. The time separation between the sample and backgroundpoints could be constant or variable, depending on the width of theeluted peak. If long separation times are required for an analysis, boththe separation between the two spectra could increase with time.

In a specific approach, solvent that comes through can be let to bleedto the pump. The lower the pressure the better the reduction of thesolvent. Preferably, while the vacuum is open, the background does notmove, since at some point the background could have higher concentrationlevels than the sample. Potentially, gases contained in the backgroundspectrum being pulled out of sample gas cell could give rise to negativepeaks. To avoid negative peaks and render interpretation of the datamore user friendly, one could chose to forgo a moving background whilethe sample cell is pulled by a vacuum.

The amount of averaging for background and sample spectral file can beapplication dependent, for instance 1 min. The averaging could beincreased as the chromatography gets longer since the peaks will bebroader and require more time to enter the cell further improving theSNR or MDLs. Increasing the averaging and the skip time as time goes oncan generate better detection limits for later or latest eluters (thatnormally show the worst detection limits). Since each resultant compoundfeature will be a peak with a flat to near flat top, the resultant topcould be further averaged to wring out another enhancement of the SNR orMDL.

In many instances, the full integration approach produces the lowestMDLs. With proper detector and optical optimization, sub nanogram (ng)to 1 ng quantities can be qualitatively and quantitatively measured byFTIR for volatile, semi-volatile and near non-volatile compoundsdirectly. Experiments routinely demonstrate 0.5 to 5 ng absolutesensitivity and lower (e.g., 10 to 25 times lower) levels could bepossible with an optimized sample cell. Since large samples can now beprovided to the instrument without damage to the analyzer and sincesamples are in many cases already concentrated, this technology will beable to measure in the parts per trillion range or lower from theoriginal sample. Using thermal desorption tubes (TDTs), the techniquesand equipment described herein, can detect single digit ppt levels ofsemi-volatile VOCs or SVOCs. With further optimization, detection limitsare expected to reach the ppq range for these types of materials.

The carrier gas flow can be interrupted for stop-flow measuring. In someinstances this may require user monitoring, e.g., by the operator. It isbelieved that this approach presents particular benefits for the fullintegration mode, since even longer averages of spectra can be obtained.In one example, the flow into the sample cell is stopped, while thecolumn flow continues. At specified intervals, e.g., every 30 or 60seconds, the valve opens briefly, for 10 seconds, for example, to dumpthe next plug of gas into the sample cell.

In another approach, stopping the flow of carrier gas is also possible,using a suitable arrangement.

For mixtures that include solvents, the solvent may be vented before theseparation device, after the separation device or allowed to flowthrough the sample cell. In a semi-volatile analysis, for instance,volatile species come off first and could be either diverted at aspecially configured injection port or after the separation device fromthe sample cell, or the sample cell could be maintained under vacuumremoving the volatiles into the vacuum system until it is desired tomeasure for semi-volatiles. PVT or PTV devices also could be employed.

In some embodiments, the sample is concentrated to obtain determinationsto low parts per trillion or high parts per quadrillion levels. Forsemi-volatile or near non-volatile materials (e.g., pesticides,herbicides, dioxins, explosives, nicotine, mold, mold sources, and soforth) MDLs could be in the parts per quadrillion (PPQ) range. Measuringin the parts per quadrillion range can allow detection of nearly anysemi-volatile chemical in a sample.

Suitable concentration techniques include, for example, those based onthermal desorption tubes (TDTs), purge and trap, solvent concentrationapproaches and others. A TDT AirScan® system, for instance, relies on amulti-matrix sorption tube developed by Prism Analytical Technologies,Inc., U.S.A., that is designed to trap a wide range of compounds (bothpolar and non-polar) from the air. After sampling, the sorption tube canbe submitted for qualitative and quantitative identification of over400+ compounds.

In some cases, a TDT used to collect VOCs or SVOCs could be run forlonger periods of time to significantly concentrate semi-volatiles. Forinstance, if a sample cell is 200 mL in volume, the amount of airconcentrated can determine the concentration capability. For example,collecting 24 hours of air at 200 mL/minute (min) would result in a 1440fold concentration. Since volatiles can move on and off the TDTs, theyare not expected to overly concentrate and low ppt or even ppq levelsmay be possible for semi-volatile compounds. This would now allow for adirect ambient air measurement of materials that are normally monitoredusing collected dust samples (solvent extracted, concentrated theninjected) which are notoriously inhomogeneous and can provide verybiased results. If this GC-FTIR technology has a base sensitivity of 1ng for a pesticide (or any semi-volatile), taking a sample with a 1440fold enhancement would potentially allow for approximately 3.5 pg/L of apesticide or herbicide or similarly low volatility compound to bedetected. For a compound with a molecular weight of 250 g/mol, thedetection limit would be approximately 500 parts per quadrillion (ppq).Potentially, both numbers could be lowered, e.g., by a factor of 2.5,with a sampler running at 500 mL/minute, or potentially higher.

Various steps in the method described herein can be conducted manually.In specific embodiments, at least one and preferably more or even allactivities are automated and performed by the computer system 34 thatcan be connected to or integrated with system 10 or one or more of itscomponents. In specific implementations, the computer system 34 isconnected to or integrated with at least one of the FTIR spectrometer,the GC and the FTIR detector being employed. Computer system 34 monitorsand/or controls the pressure in the sample cell 14. It preferablycontrols the operation of the vacuum pump 18 and various valves 24, 26A,26B. The computer system 34 further preferably monitors the pressuredetected by the pressure sensor 20 and/or the output of othersensors/transducers. In specific examples, the computer system 34accesses internal or external libraries, and/or other devices or sourcesneeded for data collection and analysis. In the embodiments of FIGS. 2Aand 2B, for example, computer system 34 controls the operation of the GC12 and receives the spectral information generated by the FTIR 16. Thecomputer system 34 further controls the operation of the vacuum pump 18and receives information from the pressure sensor 20 and detector 22. Inother embodiments, computer system 34 controls valves 24, 26A and 26B.

Specific aspects of the invention utilize sample handling,detection/monitoring devices, and controls operated by the computersystem, software executed by the computer system, and libraries andother information stored on the computer system, and so forth in orderto execute at least some of the following functions:

-   -   monitoring retention times (RT) of GC;    -   evacuating the gas cell to a specific vacuum pressure and        optionally sealing it;    -   determining what vacuum is needed to gather all gas into the gas        cell without pressurizing the cell and affecting GC;    -   measuring in absolute mode so the gas cell pressure does not        affect the resulting measurement;    -   coupling the GC exhaust to the FTIR gas cell directly;    -   monitoring the pressure of the gas cell intermittently or,        preferably, continuously;    -   integrating the peak signal, thus providing significant SNR        improvements over current technology;    -   averaging each peak by measuring the compound repeatedly after        it stops coming off the GC;    -   managing FTIR spectral data to control the output data stream;    -   determining which of the data obtained are sample data and which        are to be used as background data;    -   determining how long a compound can be analyzed before        interferences occur rendering the measurements unreliable;    -   database searching for compounds as they come off;    -   quantifying compounds as they come off;    -   correcting for concentrations with the help of internal        standards;    -   generating calibration files for each compound;    -   developing procedures (protocols) for analyzing data as        compounds are coming off to correct for interferences;    -   determining when a new compound is eluting from the GC;    -   determining when the compound is finished emerging from the GC;    -   determining for how long a compound can be quantified after it        comes off the GC, e.g., using errors related to the measurement;    -   running multiple analyses simultaneously for different        compounds;    -   running multiple analyses for each compound to determine best        result;    -   varying the spectral regions utilized based on potential        interferences;    -   predicting MDLs as measurements are being taken;    -   determining retention time and/or retention index for future        analyses or set analyses.

Steps shown above can be repeated one or more times.

Specific embodiments utilize various detectors, actuators, hardware,software interfaces, heaters, coolers, vacuum pumps and flow control,mirror movements, sample handling or other means, or combinationsthereof, to provide instrumentation control. Elements and/or featuresthat can be controlled automatically include but are not limited toparameters characterizing the gas flow in and (eventually) out of thesample cell, the carrier gas flow, valve openings and closings, pumpoperation, pressure levels, sample injection, sample concentrationtechniques or devices such as TDT's, traps, purge systems, spargers andso forth (if such techniques or devices are utilized) and others.

In specific implementations, a control circuit managed by the computersystem 34 dynamically controls the sample cell pressure. For instance,automated valves can be set to pull a vacuum on sample cell 14 beforestarting a run. Pressure levels in the cell can be controlledautomatically as well. In many cases, isolating sample cell 14 from pump18, thus allowing gas to accumulate in the sample cell, also isperformed automatically. Automation can be utilized to set a desiredcarrier gas flow of N₂ (or other carrier gas) from the separator, e.g.,GC 12, into the sample cell, to isolate the cell from the carrier gas,to divert the carrier gas to any secondary pumping station, to switchthe flow to the FTIR gas cell for sample collection, and so forth.

With respect to data handling (e.g., data collection and analysis), aprocess carried out in a system such as, for example, system 10 of FIG.2B can involve: data collection, data integral/differentiation/signalaveraging, data spectral deconvolution/quantification; data reporting;and others. Each function can be controlled through methods such asfurther described below.

In one example, a suitable configuration for data collection has aresolution (with cosine apodization) of 4.0 cm⁻¹. As known in the art,apodization can be used to change the shape of a mathematical function,an optical transmission or a mechanical structure. In the system andmethod described herein, apodization is particularly important forobtaining spectra without artifacts when very low noise spectra aredesired. For example, an apodization function that goes to zero appearsto make a significant difference in baseline artifacts. Valuableinformation also can be obtained using higher or lower resolutions. Insome cases, protocols are used for calibrations that are stable frominstrument to instrument or over time. For instance, constantcalibration of the detector can be implemented with a suitable detectorlinearization algorithm.

An illustrative configuration has about 34 co-added scans that can takeabout 5 seconds. Sampling time could be shorter or longer depending onthe separation technology utilized. In some cases, better resolution ofthe data is obtained using shorter time periods, 2 seconds, for example.Even with data averaging, the peaks appear narrower and somewhat betterresolved. So a default or initial run can be conducted 1 to 2 seconds.

Calibration data can be provided for each compound, and, in specificimplementations at multiple concentrations. Retention index per compoundcan be determined using hydrocarbon reference standards or utilized fromcurrent mass spectral library data. For instance, retention index dataare available from many sources, as known in the art, and are typicallyprovided based on the type of column being utilized. Calibration datacan be called when a certain index is reached, e.g., for thedeconvolution described below. An initial prediction could be performedto determine which compounds within a retention index window mightactually be present. This initial screening will limit the number ofcompounds then utilized in the multivariate analysis.

Data integral/differentiation/signal averaging functions can utilize,for instance, a 1 minute moving spectral average. Time spacing betweenbackground and sample spectrum can be varied.

Data spectral deconvolution/quantification can be provided by a movingmultiple linear regression based on compound retention index. A newregression matrix can be built for each spectrum analyzed in real time.Compounds selected for each regression are present for a relativedistance +/− of its own retention index. Very high concentrationcomponents, internal standards or solvents can be present in a selectset or in all regressions.

Multiple region analysis for optimal fit and analysis can be employed.For example, software can be designed to select one, more or allabsorption regions present in an IR spectrum for optimized analysis andprecision. In specific examples, the software is set to manually selectall the compounds to be analyzed and their respective analysis regionsto be used.

Data reporting can include information such as compounds identification,compound retention index, compound retention time, level of sampleconcentration, original concentrations of sample (before concentration),“goodness” of fit of spectral match.

In many implementations, data analysis is conducted during the datacollection process. In specific examples, the process includes one, moreor all of the features described below.

The process can begin with evacuation of sample cell 14 to a specificpressure, e.g., a pressure selected from the range of from about 0.001atm to about 0.8 atm. A typical transducer utilized can measure up to1.3 atm. N₂ can be used as the fill or carrier gas.

Standard drivers for the spectrometer's computer system can be utilizedduring spectra collection, a process that typically includes obtaining abackground spectrum. In many cases, this background spectrum is anaverage of spectra determined by the computer system for ˜1 and 2minutes.

IR spectra will then be collected by the computer system at a nominalspacing, for example, every 5 seconds. While the spacing could changeduring the experiment, this is not necessary since the data will beaveraged after collection by the computer system. Typically, therefore,spectra can be collected at the same spacing from beginning to the endof the sampling, with 2 seconds providing good resolution in many cases.

Again, each reported spectrum will be an average of IR spectra over thattime frame. While the same number of data points will be present, afterthe initial few data sets they will be averaged spectra determined bythe computer system. Averaging can take place in Igram, Single Beam orAbsorbance space and comparisons can be undertaken to determine whichresults in the best SNR by the computer system. A single beam spectrumreduces computational requirements by not needing a FFT (fast Fouriertransform) to occur each time, thus providing more time for thequantitative algorithm to be developed and utilized.

The average time used can be determined based on the speed of thechromatography, separation or distillation either automatically by thecomputer system or by an operator. In many cases tests can be conductedusing 1 minute averages. Other time periods can be employed. Forinstance, the averaging time could be shorter for faster chromatographyand could be set by the user or based on the time length of data. As thechromatography gets longer, the peaks may exceed 1 to 2 minutes inlength and longer averaging times might occur, determined by retentiontime or some other factor like retention index or by analysis of thedata by the computer system.

If the data are collected by a FTIR, the raw interferograms will besaved by the computer system as well, since the interferograms can allowfor additional processing of the data without loss of SNR. To reduce theneed for redoing the FFT, the single beams can be saved as well.

The resolution can be anywhere from 0.25 cm⁻¹ to 32 cm⁻¹. A smallerrange is 2 cm⁻¹ to 8 cm⁻¹ is used in some examples. Currently, about a 4cm⁻¹ resolution, for example, appears to balance the need to separatesimilar compounds, while achieving high SNR.

Once the spectral averages are generated by the computer system, ratiosbetween the initial minute or two of data against the originalbackground can be obtained. The resulting absorbance spectrum can beanalyzed by deconvolution software executing on the computer system. Toavoid complications associated with negative peaks, the movingbackground is not started until the sample cell is closed and the samplebegins to integrate.

After some point (e.g., 1 to 2 minutes into the data collection) thebackground will begin to move with the sample and a new background canbe used against a new sample spectrum to generate the sample absorbancespectrum by the computer system. The separation of the background andsample will then be in time, a time that could be fixed at 1 to 2minutes or can be varied with the length of data collection.

In a case in which a peak is 3 minutes wide, the computer system uses abackground that is more than 3 minutes prior to the end of the peak inthe original chromatograph. Thus the chromatography, separation ordistillation will most likely determine the spacing between thebackground and sample.

In this procedure any compounds that are present in the current (moving)background will be eliminated from the data by the computer system.Thus, compounds that enter the sample cell before the background will bezeroed out, as will compounds that come in during the background. Onlycompounds that come into the sample cell after the background will showup in the resultant absorbance spectrum that is calculated by thecomputer system. This simplifies the deconvolution data analysisalgorithm executed by the computer system since the algorithm only needsto analyze the compounds that could be present at that time.

The relationship between the degree to which the separator resolves thespecies in time (for instance the length in time of the GC peaks) andthe period used to calculate background spectra can be determined invarious ways.

In many cases the background is considered to be at least 1 to 2 minutesin length. Thus at the beginning of starting the carrier gas or for theevacuated gas cell the background will last until some point in thefuture. Since spectra are stored every few seconds by the computersystem, steps performed manually or automatically can be redone with adifferent set of parameters after the data are fully collected. So, thesoftware executing on the computer system, the operator or both havemany opportunities to optimize the results.

In one approach, raw data can be collected to determine the time periodrequired for large compounds to elute at each point in time. This canalso be accomplished by relying on internal or external standards. Thedata collected provides information about the chromatography goingforward. So, at retention index (RI) 300, one setting for thebackground, another skip, then sample spectra, at RI 400 another and soon. Since the raw data already exists and the large peaks show up asintegrated masses, one can check on each data set before, during orafter the analysis.

Another approach is completely dynamic, with the software executing onthe computer system starting an initial time e.g., 1 minute background,2 minute skip, 1 minute sample. Then the software performs anoptimization. Once the peak gets no taller or reaches a consistentplateau for certain time period, it can be concluded that the correctbackground and sample integration time have been chosen. This approachis based on actually observing the compound and might also allow foroptimization of the background spectrum selection. The closer thebackground spectrum is in time to the sample spectrum, the fewerinterfering species to deal with during the multivariate analysis. Thisshould produce a much better quantitative result.

Yet another approach uses the van Deemter and related equations topredict the width of the peaks moving forward from the internal orexternal standards. The van Deemter equation relates the resolving power(HETP=height equivalent to a theoretical plate) of a chromatographiccolumn to the various flow and kinetic parameters which cause peakbroadening, as follows:

${HETP} = {A + \frac{B}{u} + {\left( {C_{s} + C_{m}} \right) \cdot u}}$where: HETP=height equivalent to a theoretical plate, a measure of theresolving power of the column [m]; A=Eddy-diffusion parameter, relatedto channeling through a non-ideal packing [m]; B=diffusion coefficientof the eluting particles in the longitudinal direction, resulting indispersion [m² s⁻¹]; C=Resistance to mass transfer coefficient of theanalyte between mobile [m] and stationary phase [s]; and u=LinearVelocity [m s⁻¹].

Other possible options involve using set parameters throughout.

The deconvolution algorithm executed by the computer system is designedto analyze the resultant spectra to determine the chemicals present andtheir respective concentrations. In specific implementations, each gasto be analyzed has a stored calibration spectrum in the computer systemthat will be used to identify and quantify its presence. Known IRdeconvolution algorithms can be used or adapted. Examples of suitabledeconvolution techniques include but are not limited to those based onmultiple regression analysis, linear or non-linear regressions, leastsquares analysis, partial least squares (PLS) analysis, inverse leastsquares analysis or other approaches.

Most FTIR computer analysis algorithms select several compounds ormixture of compounds to analyze, for example, 2 to 20+ compounds ormixtures. The analysis can involve selecting a region of the spectrum toanalyze each gas (where it absorbs). This step can be preset or selectedby the computer system based on potential interferences. Multipleregions can be used for each compound to get more quantitative precisionand a better qualitative prediction. For example, if a compound has twoabsorption bands of equal strength where one absorption band is presentin the sample spectrum and the other is not, it cannot be the gas inquestion.

A mathematical matrix or matrices is/are created to analyze for eachcompound, with some instruments creating just a single matrix andanalyzing all the gases simultaneously. Other instruments analyze eachcompound individually, so that the potential interferences are minimizedand such that one compound does not affect the analysis of another. Inyet other instruments a compound is analyzed in multiple regions and theresults are compared to determine the true presence and concentration.

In many instances, identifying more than 25 compounds from a singlespectrum can pose software difficulties. For instance, having 25unknowns requires 25 independent equations. Often, however, the numberof unknowns is considerably reduced by the fact that not every gasabsorbs in the same spectral region, with maybe only a few (2 or 3)absorbing at any one spectral location.

Unlike GC-MS, gas phase IR (and, in fact, any optical spectroscopy)absorbance spectra from multiple compounds add linearly to each other.Thus if there are two gases absorbing in the same frequency range, eachabsorbance is independent or nearly independent of the other and what isobtained is the sum of the two spectra at each frequency.

In specific implementations, the algorithm used by the computer systemwill be configured to change the compounds being analyzed based on theirexpected chromatography. Generally, the technique can analyze as many as25 or so compounds and as few as one. Since components do not need to becompletely separated, the GC utilized can be simplified or replaced byless effective separation equipment, for instance by a separator basedon distillation principles. Also, since we are quantifying each compoundindividually the interfering compounds do not necessarily need to be100% accurate since they are only present in the matrix analysis to helpdetermine the current analyte correct concentration or mass.

If gas chromatograph 12 is replaced by a pseudo distillation apparatus(further described below), the calibration data would have a temperatureterm added to their library reference file to determine when they wouldbe expected to come off and be analyzed.

During the analysis protocols, each compound can be run against a set ofstandards to determine its retention index, a parameter usually based onthe carbon ladder. For instance, if the compound elutes half way betweenbutane (C4) and pentane (C5), it would have a retention index of 450. Inthis manner, the retention time can change over time or from instrumentto instrument but the compounds will come off at the same relative timeto standards in the sample. The retention indices for many compounds canbe found in the literature or mass spectral libraries.

Internal standards can be used to set time stamps and/or to ensure thatthe sample size is consistent. For instance, when a syringe draws up asolution, it can inject not just exactly 1.0 microliter (μL) but alsovolumes slightly higher or lower, for instance 1.1 μL or 0.9 μL. Theinternal standards add in known volumes to the sample can improve theaccuracy and precision of the measurement by correcting for slightchanges in injection volumes.

As the chromatography gets to a certain retention index, the compoundsthat could elute near that time will be added to the prescreening and/oranalysis algorithm by the computer system at that point and the numberof compounds and the compounds analyzed will be different from point topoint in the data. As gases are added and removed, optimizations of thedeconvolution might occur. Thus one might measure for a compound in oneregion with one set of interferences and in another region with otherinterferences. Once a compound is no longer observed and/or it isoutside the retention index window, it would no longer be used in theanalysis (unless it is a high concentration component that might varyslightly with time) by the computer system. Since 1 to 2 minute averagesof each gas concentration are available, each peak can be at a nearconstant concentration for this time and the average of that data willbe the reported concentration. A pseudo chromatogram can be obtained byjust looking at maximum peaks showing up as the compounds come off andplotting that versus time. The plot looks similar to what achromatographer would normally see. An example for a 60 component mix ispresented in FIG. 12A, top graph 1210. This plot shows peaks as afunction of run time. It just shows the elution of the compounds fromthe column. There is no long skip or average on here so the peaks do notflatten out, but the graph would be something a chemist could look at itfor compounds. The bottom graph is the spectrum, optical spectralresponse related to the point in time 1214 (35 minutes). The featuresbetween 700 and 1300 cm-1 are from the compound(s) that are peakinghere.

Any large concentration compounds found (e.g., solvents that may bepresent) may stay in the analysis algorithm long past their presence(retention index) just in case the concentration changes slightly. Smallchanges in large concentration compounds will then be monitored andprevented from interfering with other analyte gases as they elute.

Using the techniques described above, having 50 or so retention indexsegments and analyzing for 20 compounds per segment, can allow handling1000 compounds per analysis automatically by the computer system.However, each sample point could be a separate retention index and manycompounds may be removed due a prescreening algorithm, so 1000's ofcompounds could be measured or eliminated during each analysis. Since IRspectra are physical constants, any gas in the IR library can beaccurately determined both qualitatively and quantitatively. Sinceintegration is carried out, the chromatography separation is eliminatedfrom the measurement. Thus whether the peak comes off fast or slow, theresult is the same as long as the skip time is long enough.

In some implementations, protocols and/or algorithms are designed tocorrect for pressure broadening. Pressure broadening can be observed inthe spectra of some compounds when the pressure changes. Typically, thelighter the molecule, the more pronounced the effect. In one example,the pressure at which a compound is detected is measured by a pressuretransducer 20 for the sample cell 14 and is recorded by the computersystem. The pressure transducer can be, for instance, pressure sensor 20in FIGS. 2A and 2B, or another pressure sensing device, not shown in thedrawings. Additional spectra can be obtained over a range of pressures.For instance, a first spectrum could be taken by the computer system 34when the analyte gas is fully present in the sample cell at a lowpressure at the onset of the analysis, as the sample cell just begins tofill with gas. Subsequent spectra can then be taken by the computersystem 34 at increasingly higher pressures, as the carrier gasaccumulates in the sample cell. Similar data can be gathered for othercompounds to generate libraries of pressure-related calibration spectraby the computer system 34. The data can then be used correct forpressure broadening effects. For example, it can address uncertaintiesin the quantitative analysis of very light molecules such as methane(CH₄), caused by a varying pressure in the sample cell.

In specific implementations, the temperature of the sample cell willremain constant since temperature variations can affect the absorptionspectrum as well.

Once certain compounds are identified and quantified or potentiallybefore spectral analysis as a prescreening technique, a goodness of fit,using, for instance, multiple spectral regions, can be performed to givethe likelihood that the peaks observed in the collected spectra are thecompound identified or compound in question. Reporting the compound canbe accompanied by the percent likelihood that it is indeed the compoundas part of the result. In many cases, a 95% or higher may indicate thatthe compound identified is the correct compound.

Since the resultant data will not be a normal chromatogram (a singlecontinuous line of data containing peaks versus time), reportingsoftware will be very important to understanding the data set. Inspecific examples, after all the processing, the data can be presentedby the computer system as follows. As already mentioned, a pseudochromatogram using the high points in the spectrum as a function of timeis shown in plot 1214 of FIG. 12A.

First, a user selects the gases for which a report is desired (e.g.,based on a specific method or EPA requirement). Alternatively, all thecompounds found can be selected for the report by an analysis of theentire spectral library.

A limit can be set to decide which compounds are to be presented in thereport. If every compound in the library is targeted for analysis, everycompound will have a predicted concentration. The average concentrationfor each compound over the 1 to 2 minute interval will be used for thereported concentration. The limit for reporting (as concentration or ng(mass) level) could be set prior to the analysis as a global level, foreach gas in the library depending on the levels at which it is normallyseen or it relative toxicity levels.

One illustrative reporting pattern includes: retention index, compoundname and/or its registration or CAS number, chemical formula, chemicalstructure, mass or concentration of sample analyzed (ng or ng/L), massor concentration from original sample (taking into account any furthersteps to concentrate the sample) and likeliness that the compound ispresent. If unknowns to the library are found they could be listed bytheir retention index along with the features identified and likelinessthey contain a certain functionality (alcohol, ether, ketone, etc). Oneillustrative reporting method has mass (ng) or concentration on they-axis and compounds shown as a single line (bar graph) at theirrespective R.I. (Retention Index), resulting in a chromatogram that isng/RI, with the peak having no time length associated with it. Anexample of this graph is shown in FIG. 12B. Thus the report shows thepeak reading in a bar graph form. Unknowns could show up where the R.I.is with an estimate of ng or concentration based on the type of compoundpresent.

The reporting software executing on the computer system can also allowfor inspection. For instance an interface can be provided to link acompound listed in a report to the spectra and mathematical matrix usedto identify and quantify it. In further implementations, library spectracan be overlaid on the sample spectrum on a video monitor operated bythe computer system to show the match. If desired, further softwaremanipulation could remove identified interfering compounds so that onlythe compound of interest is observed in the spectrum. Data reporting canalso include user interfaces generated by the computer system thatoverlay and/or compare spectral data between a peak feature in a pseudochromatogram, or any spectral feature at any point in the pseudochromatogram, and compounds that could be present.

A feature important to many of the embodiments described here is acalibration library maintained by the computer system. With its use,calibrations only need to be collected once by the computer system (fora specific type of FTIR, spectrometer, laser system) and could beintegrated with the spectroscopic component used, regardless the type ofseparator (GC, pseudo distillation, etc.) to which it is connected. Alaboratory with multiple “like” instruments could rely on the samecalibration, reducing or minimizing the need to calibrate the variousinstruments.

To obtain the calibration library, each material is measured on a GCwith potential columns and stationary phases and compared to standardsto determine its retention index. Alternatively, the retention index foreach material could be acquired from the literature or mass spectrallibraries. All this information once obtained is added to the file forthe compound, a file that may further include a reference to boilingpoint, a temperature reference for distillation purposes, retentionindex based on column stationary phase type and, if desired, othercharacteristics of the compound.

Each material is also added to the sample cell at a couple of masses orconcentrations (calibration curve) and multiple pressures to correct forpressure broadening effects (if such effects occur). The spectralregions for analysis can be set by the instrument manufacturer, by theuser or automatically, e.g., by specific software. Quantificationregions can be included, as can other spectral regions in which thecompound absorbs, to enable the software to rely on the information forany compound that is using that absorption region for quantification.

A calibration curve can be generated so that a quantitative regressionanalysis (e.g., linear, quadratic, or, as needed, cubic or quartic) canbe performed.

Similar approaches can be developed for transient mode flows or forother flow arrangements that allow the averaging/integration of spectralfeatures taken over a time interval, for instance a window determined bya width of one component in the output emerging from the separator.

FIG. 4A is a flow diagram illustrating the control of the system 10 bythe computer system 34 and specifically how absorbance spectra aredetermined over the processing run of the separator 12.

Before the separator, e.g. GC, 12 is started, valve 24 is opened and thevacuum pump 18 is operated to evacuate the gas cell 14 to low pressurein step 110. In general, lower pressures in the sample cell 14 producecleaner background signals, but low pressures are not necessary. Infact, in a different configuration, the output of the separator 12 couldbe injected into the sample cell 14 under pressure, avoiding the need todraw a vacuum, for example.

Then, in step 112, the computer system 34 waits for the start signalfrom the separator 12. When start signal from the chromatography system12, for example, arrives, the start time T₀ is set to the current timein step 114. Additionally, the valve 24 is closed to thereby seal thegas cell 14 in step 116.

Additionally, in step 118, the current single beam spectrum is set asthe background single beam spectra B₀ for the start time T₀.

The system 10 then collects the spectra S_(x) for the current timesT_(x). These are single beam spectra that are generated by taking theraw interferograms from the FTIR spectrometer 116 and then convertingthose interferograms to intensity versus wavenumber spectra.

In other situations where a different spectrometer technology is used,the intensity versus wave number spectra might be directly read-out asin the case of a post dispersive system, or simply be a function of thetime response of a detector, in the example of a tunable optical source(laser) spectrometer.

In step 122, it is determined whether or not the system has beencollecting spectra for longer than Skip Time. Generally, Skip Time maybe about 10 seconds to as long as 5 minutes. It is typically betweenabout 20 seconds and 2 minutes, however.

If the difference between the current time T_(x) and the start time T₀is not greater than the Skip Time then the absorbance spectrum iscalculated in step 128. Here, the absorbance spectrum A_(x) is based onthe negative log (base 10) of the current spectrum S. at the currenttime T_(x) divided by the single beam background spectrum B₀ detected atthe start time. A_(x)=−Log₁₀(S_(x)/B₀).

In step 130, the computer system 34 determines whether or not theseparator 12 has completed its run. In the situation where it has not,then processing returns back to step 120 and the new current spectraspectrum S_(x) is obtained for the current time T_(x).

When the loop has been running for longer than Skip Time as determinedin step 122, then the background spectrum is set to the spectrum thatwas detected previously based on the delay set by Skip Time in step 124.In the example where Skip Time is 60 seconds, then the currentbackground is set to the spectrum that is 60 seconds old. That isB_(x)=S_(X-SKIP).

Then in step 126, the current absorbance spectrum A_(x) is calculated asA_(x)=−Log₁₀(S_(x)/B_(x)).

FIG. 4B is a flow diagram illustrating the control of the system 10 bythe computer system 34 according to another embodiment, which implementsa solvent delay.

In general, many of the steps in this new flow diagram are similar tothose in the previous diagram. Main difference is the implementation ofthe solvent delay in step 140. Specifically, the system runs with thevalve 24 open and the vacuum pump 18 running for the “solvent peakdelay” time period (Solvent Delay). This allows for the solvent (in thecase of liquid injection) to flow from the column of the GC separator 12to the gas cell 14, then out through the vacuum pump 18.

In some embodiments, during this “solvent delay” period, the system 10continues acquiring and storing single beam spectra. The system 10 willalso begin computing absorbance spectra=−Log (current singlebeam/background single beam). The computer system, by analyzing thesespectra, can also determine when the solvent has been removed from thesample. It is also possible that the solvent could be diverted near orat the injection system depending on the sample and configuration, sothat it never enters the GC column or enters a small length and then issplit off.

FIG. 4C illustrates the operation of some additional embodiments. In theprevious discussed embodiments of FIGS. 4A and 4B, the absorbance at agiven time is calculated based on the current detected spectra and apreviously calculated background. In this current embodiment theabsorbance calculations of step 126 are based on a current average ofspectra and a background that is also typically calculated based on anaverage of spectra.

The plot represents the concentration profile in the cell 14 as acomponent comes out of the GC column or other separator and goes intothe gas cell 14. Since the cell 14 integrates the components, i.e., issealed, the concentration increases until the whole peak has reached thecell (see point 152). At that point in time, all of the component (e.g.,compound) is in the cell 14. And, this event can be determined by havingthe computer system 34 monitoring how the spectra change over time andnoting when successive spectra are undergoing little change with respectto each other. This can be performed in real-time or in a postexperiment analysis.

Now the sample single beam spectra can be signal averaged for a periodof time 154. Exemplary average times are generally between 10 secondsand 5 minutes, although they are more commonly between about 30 secondsand a few minutes. The start of this averaged spectrum is indicated bythe elution time. Then the background is taken from a similartime-averaged signal 156 based on spectra that were taken before theelution of the peak into the cell 14.

The resulting absorption spectrum will contain only features due to thecompounds that have been collected in the cell during this time.

Here, skip time would likely be chosen to be equal to or slightly largerthan the time required for the chromatographic peak to elute completely.This would result in the background spectra being acquired before thepeak begins to elute, and the sample spectra being acquired after thecompound has completely eluted.

In general, the Skip Time can be fixed for the entire chromatographyrun, or it can be increased later in the run when chromatography peakare typical broader (the time required for the peak to completely elutefrom the column is longer due to diffusion during the residence time inthe column). Normally, this results in reduced sensitivity since thebroadened peaks have reduced peak intensity. With the present approachthis is not the case since increasing the skip time still allows for theentire peak to be analyzed in a single measurement.

The sample averaging time 154 and background averaging time 156 need notbe the same. If there are no other compounds eluting near the peak, thenbetter sensitivity can be achieved by increasing either or bothaveraging time. Even if there are other peaks that elute nearby,spectral discrimination may still allow for increased averaging time.

In other embodiments, instead of calculating absorbance from twoaveraged single beams as described above, the method could use thestored initial background spectrum from the beginning of thechromatography run, or from any other suitable time for measuring abackground when the cell is empty or purged. Then during the run, theconventional absorbance spectrum would be calculated from the averagedsingle beam sample spectrum and the stored initial background spectrum.This can be converted to the absorbance spectrum by subtracting thebackground absorbance spectrum using similar logic as described abovefor average and skip.

In practice, it is not known when the peaks will actually elute. Thus,in a one mode of operation, spectra will be acquired and stored duringthe run with a fairly short time interval, for example 1-2 seconds.Every 1-2 seconds a new absorbance spectrum can be calculated using theskip and average parameters, which can be fixed for the whole run, orvarying with time as the run proceeds. Faster spectral data collectiontimes in the range of 0.1 seconds are certainly possible for very fastGC experiments or when required due to the complexity of the sample.

In general, post analysis can also be performed, and this allows foroptimization of skip and average parameters for specific chromatographypeaks, or for specific eluting compounds. It may be advantageous to testresults using longer or short skip time to be sure the whole peak hasbeen capture by the current skip time. It may be useful to test longeraveraging time in order to achieve more sensitive detection. It may beuseful to test shorter averaging time in order to better rejectinterfering species that elute near the peak of interest. This logicallows the analysis to be optimized once an initial chromatogram isknown.

FIG. 4D shows the analysis used to obtain the chromatographic results.

In more detail, in step 160, the retention index RI is calculated forsample times Tx. Then, in step 162, an input spectral library 170 and aninput component list 172 are accessed. In general, the system willsearch for the components of interest by referencing the spectrum forthose components.

Calibration spectra of the library 170 are stored for pure componentcompounds with the corresponding concentrations, desirable spectralregions for analysis, and spectral regions where there might be spectralinterference with other compounds. Calibration spectra can also bestored with the retention index for the compound, which is an indicatorof when the compound can be expected to elute from the column.

The computer system 34 usually selects a subset of the librarycalibration spectra and then performs quantitative analysis in step 164to determine the concentration of these components. The quantitativeanalysis can be improved by excluding compounds from the library thatare not present in the sample spectrum. The results are reported in step166.

This can be done indiscriminately for each absorbance spectrum, thusproducing results that look like a typical chromatogram. This can alsobe done by targeting specific compounds. In this case, it is desirableto choose the proper subset of the calibration library, and also to findthe correct elution time, skip time, and average time for the analysis.

The first approach to choosing a subset of the library is based onelution time or retention index. Since the approximate time that a givencompound in the library will elute from the column is known, thecomputer system 34 starts by only considering compounds that are likelyto elute for the elution time of the sample spectrum being analyzed.

There will also be compounds that should be included over a larger rangeof time than the expected elution time. For example, water and carbondioxide may always be present, and the solvent used for liquidinjections and high concentration components may be present in thespectrum for several minutes after the solvent peak starts eluting.Further components are also monitored for decreases due to condensationso that they do not interfere with analysis. They would show up as anegative concentration.

After reducing the list of possible compounds, quantitative analysis onthe sample spectrum is performed by the computer system to determineconcentrations of these compounds in the sample spectrum. If any of thecompounds are determined to not be present, then they are removed fromthe list and the analysis can be repeated with the further reduced listof compounds. Alternatively, the list can be tested one-by-one beforeanalysis to determine if the compounds are present. The analysis canthen be performed using the only those library component detected to bepresent in the sample spectrum.

The presentation of results by the computer system 34 is often in acompound specific chromatogram format, concentration or mass versus timefor each compound. This could also be converted to a combinedchromatogram format, concentration or mass versus time for allcompounds. In general, the peak height of each peak corresponds to thetotal concentration or mass of the corresponding compound. The peak areais only indicative of the time period during which the compound elutesfrom the column.

The results could also be presented in a “stick” plot format, where themass or concentration of each compound detected is plotted as a singlepoint versus time or retention index.

Some of the embodiments disclosed herein utilize separation techniquesthat do not rely on gas chromatography. In many cases, such techniquescan be used since procedures related to data collection, data handlingand data analysis described herein do not require fully resolvedchromatographic peaks. Particular applications that can benefit fromeliminating the use of the GC include but are not limited to analyses ofsemi-volatile and non-volatile species; analyses of some inorganics thatdo not chromatograph well; analyses of mixed samples (organic,inorganic, VOC, SVOC, non-volatile) that typically require columnchoices and/or changes; and others. Considering that GCs can be viewedas a very controlled distillation (with 10,000-100,000's of theoreticalplates), and taking into account that full resolution of peaks is notrequired in practicing aspects of the invention, a GC separator such asdescribed above can be replaced by a distillation-based or “pseudodistillation” separator, as further described below. During operation, apseudo distillation separator can first remove the highest component,e.g., the solvent. Once this is accomplished, the quantitative levels ofchemicals that can be measured decreases linearly with the increase inthe sample size.

Shown in FIG. 5, for example, is distillation-based separator 50 that isused in place of the gas chromatograph (GC) separator 12 shown in FIGS.2A and 2B.

The separator 50 includes injection port 52, for receiving a sample thattypically includes a solvent, sample vaporization chamber 54 andcomputer system 56 monitoring and/or controlling the temperature.

In many implementations, sample port 52 is configured to accommodaterelatively large injection volumes, e.g., of the order of milliliters(mL), such as 1 mL, rather than the typical 1 μL sample common withGC-MS injection volumes. The port can be maintained at a temperaturesuitable for removing the solvent and retaining the compounds ofinterest.

A relatively small tube, e.g., ⅛ inch, 1/16 inch OD, that is a fewinches long, preferably fabricated from stainless steel or anothermaterial (metal, alloy and so forth) with the potential of an inertcoating, having low heat transmission properties, can serve asdistillation column 58. Typically, such an arrangement is capable ofseparating components without problems stemming from chemicalinteraction with the mobile or stationary phases typical ofchromatographic separations. The tube can be hollow or can contain apacking material, e.g., glass beads. Interior surfaces of the tube canbe smooth or roughened to increase the number of theoretical plates. PVTor PTV can be used to perform a similar function.

Taking advantage of the poor heat propagation through the tube material(stainless steel for instance), heating the vaporization chamber 54 tohigher temperatures than tube 58, e.g., 300° C., generates a gradienttemperature that extends along the tube, to the sample port 52. Thischange in temperature along the length of the tube is expected togenerate a large number of potential “theoretical plates” inside thetube 58. Raising or lowering the temperature applied to 54 and 58determines which materials come off the column. The number of“theoretical plates” could be determined by separating a number of VOCand SVOC mixtures. The information can then be used to optimize theheating configuration.

Heating and cooling can be conducted using a thermoelectric (also knownas a Peltier) device (the principle of which relies on heat transferfrom one side of a solid state device to the other, with consumption ofelectrical energy). By changing the DC voltage the device can beswitched from cooling to heating to remove the solvent and eventuallythe compounds initially present in the solvent.

The temperature of the heated transfer line 60 also can be raised sothat heating is on both sides of the column 58 which would change thedynamic of the temperature profile across the column 58. The column maybe provided with a jacket not shown in FIG. 5 that can be pulled overthe column 58 from the hot vaporization chamber end 54 to heat the wholetube to a certain temperature in order to remove compounds with thehighest boiling points.

Heated transfer line 60 connects distillation separator 50 to the samplecell 14 described previously with a suitable detection and/or analysisdevice, while conduit 62 provides optional carrier gas flow. The sampletypically including a solvent can be introduced via syringe 64.

A distillation-based (or pseudo-distillation) separator such asdescribed above is connected to the sample cell 14. The spectraldetection/analysis device such as an FTIR, another optical spectrometeror detection means is then used to analyze the components in the cell 14as describe above. In some cases, it can even be coupled to a MS device(particularly if sufficient theoretical plates can be generated toproduce adequate peak separations).

In other implementations, the exhaust of the pseudo distillationseparator is connected to a GC, for instance GC 12 in FIG. 2. In thelatter case, the pseudo distillation separator can be used, forinstance, to vaporize solvent while capturing volatiles and semivolatiles in the tube. The retained compounds can be then separated bythe GC.

Shown in FIG. 6 is high volume injection assembly 80 includingsepta-containing injection port 82, typically held at low heatconditions, and stepped vaporization chamber 84, first eluting thesolvent and then quickly vaporizing all the analytes. The sample can beintroduced via syringe 86. Again, this can be similar to PVT or PTV.

Conduit 88 provides septum purge and column flow gas. Valve 90 can beused to vent vaporized solvent or direct the vaporized solvent to asolvent capture system. The sample is then directed to sample transportvalve 92 from which it can pass, via conduit 94, to a separation devicelike a GC with a detection and/or analysis device described herein.Conduit 94 can be provided for secondary column flow for the GC or otherseparation device during the sample preparation process.

In another possible arrangement, solvent vapor is analyzed for solventand solute content. In this implementation, the exhaust of valve 90 isdirected to the FTIR to determine what is coming off with the solvent. Avalve or another suitable device can be used to divert gas from going tothe sample cell, thus preventing solvent from going backwards throughthe GC. Since generally there are not that many compounds that co-eluteor in this case vaporize with the solvent at low vaporizationtemperatures, the lack of separation is not thought to present problems.This same form of solvent diversion to the gas cell could be achievedwith a properly configured PVT or PTV.

Embodiments disclosed herein can have many applications and could beused or adapted for ambient air collection for VOCs or other chemicals,home air collection, in particular in cases in which cost is an issue,potentially for obtaining multiple samples simultaneously, personalexposure monitor in the work place or other indoors environments, forsemi-volatile analysis (pesticides, herbicides, drugs in urine,nicotine, etc.), medical tests, for drug purity testing, e.g., in thepharmaceutical industry, and others. In specific applications, thesystem described herein is connected to sample collection devices suchas TDT, liquid, solid, purge and trap or other devices, and so forth.

The following non-limiting examples are provided to illustrateprinciples of the invention.

Example 1

In a conventional GC-FTIR configuration, the gas leaves the GC andpasses through the FTIR gas cell (usually a light pipe that is generallyaround 10 to 20 cm long) in a few seconds. If the concentration of achemical compound is high enough, what is observed is a peak that risesand then falls, a behavior typical of any other detector. In contrast,using a system such as the system of FIGS. 2A and 2B, the gas can becollected in the gas cell for integration of each peak eluted from theGC.

A multiple path length gas cell can be utilized to generate a muchhigher absorbance since in the configuration described herein responsetime of the gas through the cell is not a concern. The absorbanceincreases linearly with the increased path length. Thus increasing thepath length from a length of 10 cm (the actual length of the cell) to amultiple path of 5 m will produce a 50 times greater absorbance,assuming the same concentration in the in the sample cell describedherein and a conventional lightpipe. (Typically, a light pipe will havea higher concentration since the gas emerging from the GC is not diluteddue to expansion in the sample cell.) A particular implementation thatcould result in a significant improvement (e.g., 50 times greaterabsorbance) relates to embodiments deployed for source testing, wherethe gas just flows through the multiple pass gas cell normally and gasesare measured (ppm to ppb). In comparison, a light pipe would not give alow enough measurement (high ppm at best).

While the gas is being monitored, a portion from the incoming flow oroutgoing flow can be collected and concentrated on a TDT. The TDT thencan be desorbed through the GC to get lower detection limits. Theimproved detection limit will be based on the number of cell volumes. Sofor a collection of 60 min at 200 mL/min being trapped there will be a60 fold enhancement in the absorbance if all the gases are trapped sincethe gas cell is 200 mL. A further improvement can be obtained by runningat lower resolution since the GC carries out the separation. The resultsmay be similar to those obtained with a lightpipe due to the same lowerresolution.

The more significant advantage, however, resides in the flexibility ofrunning in the direct gas analyzer mode or as a TDT/GC/FTIR. Since bothmodes are available, each can be used as needed by source testers. Thisis not possible with a conventional lightpipe.

Once the spectra are collected or even during data collection, rawsingle-beam spectra can be obtained and averaged over 1 to 2 minutes bythe computer system. (The experiment also could be conducted by usingcalculated absorbance spectra but a higher noise level might beencountered.) Increasing the time from a typical 1 sec to 1 minute canresult in about 8 times better MDL. Combining a multiple passarrangement with the integration-averaging approach described herein canmore than make up for any losses due to the increase in sample cellvolume (compared to a traditional lightpipe approach). Improved mirrorcoatings, resulting in further increases in pathlength, can provideadditional enhancements in detection limits. For example, a highlyreflective coating could allow for 40 to 80 m in the same volume. Suchcoatings are entirely feasible with a sample (gas) cell that is onlyconnected to a GC, where problems related to the deposition of dust orcompounds on the mirror are reduced or minimized.

Since the spectra for each compound are collected after the entireanalyte is in the sample cell a further sensitivity enhancement isgained from maybe 2 or 3 times for an early eluting peak to one thatcould be an order of magnitude more sensitive for a late eluting peakthat is spread over several minutes.

Based on experience with the apparatus and techniques described herein,integrating can provide an improvement in sensitivity by a factor of 3and integrating by a factor of 8, with additional benefits due to pathlength increases, to an overall demonstrated improvement of 24×.

Starting with the original background spectrum to calculate theabsorbance spectrum, the background can be changed as more and more datawere collected. So, the background data starts to move a minute or twobehind the data collection. Expressed in a different way, the backgroundspectrum occurs a minute or two before each peak. If the background isfar enough ahead of each peak, the signal should go up, level off andthen start to decrease. Eventually the background moves through eachpeak and each peak disappears into the background. Thus the gases in thebackground only need to be stable in concentration over the time used asa background (1 or 2 minutes) and not the entire experiment. While themoving background may not per se provide significant SNR advantages, itremoves the earlier compounds by folding them into the backgroundspectrum over time. This is shown in FIGS. 7 and 8 where the analytepeaks goes up, flatten out and then decrease. The flattened region maybe increased by widening the separation time between the background andsample.

As seen in FIG. 7, one compound, 1,2,4-trimethylbenzene (1,2,4-TMB) wasselected from a mixture of aromatic VOCs. When the mixture is runthrough a sample cell (not contained or integrated) having a multiplepath of 5.11 m for a few seconds, this particular compound was notdetected and all that was observed was noise. The noisy plot shown hereis an integration of the 1,2,4-TMB signal, where the compound wascontained in the gas cell for the duration of the measurement, justabove the noise level.

In the other curve of FIG. 7, the spectral data were averaged forapproximately 1 minute. In addition, a moving spectral background wasused that was approximately 1 min in length. This could be thought of astaking a derivative of the integrated signal. The results in FIG. 7demonstrate that the processed signal was 20+ times the noise level now,from data that was initially only barely above its detection or notdetected when performed in a traditional transient detectionmethodology. The results illustrate the power of the basic technique.Further improvements in MDL can be obtained by optimizations such asdiscussed above.

With detector optimization for the resolution and spectral range usedfor collecting the spectral data, the signal to noise or MDL can beimproved by a factor of 10 to 12. Practicing aspects of the inventionallows detection of 1,2,4-TMB at the 2.5 ng level.

Moreover, since the size of the sample no longer matters because thesolvent can be boiled off without affecting e.g., MS detection, muchlarger samples can be run so that even smaller absolute concentration ofthe sample can be measured. Detection of the order of 1 ppt levels orlower could be expected, depending on the compound. Thus in contrast toa conventional light pipe, which watches a peak come and go and woulddraw out the peak, the techniques described herein rely on peakintegration.

In contrast to MS, the spectroscopic technique described herein can alsomeasure different isomers of xylenes and trimethylbenzenes (as shown inFIG. 8); can measure compounds as they co-elute (MS can only handle acouple simultaneously, if these compounds have different spectra); andcan measure as many as 10 to 20 compounds simultaneously even if theyare similar.

The SNR or MDL could be optimized to detect 10's pg of elutant, withfurther possible improvements provided by appropriate mirror coatingsand gas cell configurations. Further benefits are expected with softwareconfigured so that the algorithm or protocol is constantly changing thecompounds to be detected. Since the compounds will be coming off at aspecific index or retention time, the software will know which compoundsto analyze for and when.

Also, using FTIR (rather than MS) has the advantage that all librarydata will be both qualitative and quantitatively correct. So the librarycan be used not only to identify but also to quantify. Moreover, anycalibration generated will be fixed for every system. In contrast, sincea MS library can only qualify, calibrations must be run to quantify.Typically, MS calibrations need to be re-checked frequently.

Example 2

These experiments were undertaken to demonstrate spectral aspects of thetechniques described herein. A couple of screenshots of the fingerprintregion of the IR spectrum from 550-1250 cm⁻¹ were taken to demonstratehow the spectra change after post processing as described herein.

The graph in FIG. 9 is a final raw spectrum after a mixture of 60+ gases(compounds) is collected in the gas cell. Many of the gases werechlorinated and have strong absorption peaks at the low frequency end ofthe spectrum. All the features observed below 850 cm⁻¹ are absorptionpeaks by some of the 60+ compounds. The peak PQR structure at 950-1150cm⁻¹ is indicative of the methanol which was the solvent.

Trying to analyze a spectrum for 60+ compounds with existing techniques,even when possible, proves to be exceedingly difficult, especially ifidentifying other unknowns is also desired.

If, however, protocols or algorithms described herein are applied acrossthe data and inspecting one of the later spectra shows that most of thechlorinated compounds and the solvent methanol are no longer presenteven though they are still present in the gas cell. FIG. 10 is onexactly the same x and y scale as FIG. 9, and shows how well thebackground interfering compounds and solvent can be removed by thecomputer system. Only a few small features are observed.

At this point, the FTIR multivariate analysis software and librarydatabase can be used by the computer system to identify the remainingmajor and smaller minor peaks.

If this spectrum is expanded by a factor of 10 (FIG. 11), one canobserve the infrared absorption features and these can be easilyanalyzed, especially when using a FTIR library (e.g., of 1000s ofcompounds) in conjunction with calling compounds at the appropriate timein the GC elution. Spectral searching can also be done to call spectraif needed.

Importantly, with techniques such as those described herein, it ispossible to look at high concentration as well as low concentrationcompounds that co-elute as long as the two have some difference inspectral features. Advantageously, almost all compounds, even cis andtrans isomers have unique infrared spectra.

While this invention has been particularly shown and described withreferences to preferred embodiments thereof, it will be understood bythose skilled in the art that various changes in form and details may bemade therein without departing from the scope of the inventionencompassed by the appended claims.

What is claimed is:
 1. A method for analyzing a sample, comprising:generating components from a sample; acquiring spectral responses of thecomponents over time; and comparing current spectral responses to abackground that changes with time and comprises previously acquiredspectral responses to identify and/or quantify newly generatedcomponents; wherein the current spectral responses and the previouslyacquired spectral responses are each averaged prior to the comparison.2. The method of claim 1, wherein generating components from the samplecomprises providing the components using gas chromatography, liquidchromatography, affinity chromatography, supercritical fluidchromatography, ion exchange chromatography, distillation, fractionaldistillation, thermal desorption, pseudo distillation, thermogravimetricanalysis, or a pyrolysis.
 3. The method of claim 1, wherein generatingcomponents from the sample comprises providing the components using gaschromatography.
 4. The method of claim 1, wherein acquiring the spectralresponses of the components comprises collecting the responses in one ormore of the following spectral regions millimeter, microwave, terahertz,infrared (including near-, mid- and/or far-infrared), visible,ultraviolet (UV) (including vacuum ultraviolet (VUV)), x-rays and/orgamma.
 5. The method of claim 1, wherein acquiring the spectralresponses of the components comprises collecting the responses with aFourier transform infrared spectrometry system.
 6. The method of claim1, further comprising collecting at least one of the components in asample cell and acquiring the spectral response of the components in thesample cell.
 7. The method of claim 1, wherein the current spectralresponses and the previously acquired spectral responses are eachaveraged.
 8. A method for analyzing a sample, comprising: generatingcomponents from a sample; acquiring spectral responses of the componentsover time; and comparing current spectral responses to a background thatchanges with time and comprises previously acquired spectral responsesto identify and/or quantify newly generated components; whereincomparing the current spectral responses to the background comprisescomparing current spectral response to spectral responses that werepreviously acquired by an amount defined by a skip time.
 9. The methodof claim 8, wherein skip time is between 20 seconds and 2 minutes. 10.The method of claim 8, wherein skip time is equal to or slightly longerthan the time required for a chromatographic peak to elute.
 11. Themethod of claim 8, wherein the current spectral responses and thepreviously acquired spectral responses are each averaged prior to thecomparison.
 12. A method for analyzing a sample, comprising: generatingcomponents from a sample; acquiring spectral responses of the componentsover time; and comparing current spectral responses to a background thatchanges with time and comprises previously acquired spectral responsesto identify and/or quantify newly generated components; wherein thecurrent spectral responses and the previously acquired spectralresponses are absorbance spectra that were calculated from averagedsingle beam sample spectra.
 13. A sample analysis system, comprising: aseparator that provides components of a sample over time; a spectrometrysystem that acquires spectral responses of the components; and acomputer system that compares current spectral responses to a backgroundthat changes with time and comprises previously acquired spectralresponses to identify and/or quantify newly generated components; andwherein the current spectral responses and the previously acquiredspectral responses are absorbance spectra that were calculated fromaveraged single beam sample spectra.
 14. A system as claimed in claim13, wherein the spectrometry system determines the spectral response ofthe components in the sample cell in one or more of the followingspectral regions millimeter, microwave, terahertz, infrared (includingnear-, mid- and/or far-infrared), visible, ultraviolet (UV) (includingvacuum ultraviolet (VUV)), x-rays and/or gamma.
 15. A system as claimedin claim 13, wherein the spectrometry system is a Fourier transforminfrared spectrometry system.
 16. A system as claimed in claim 13,wherein the separator is a gas chromatography system, liquidchromatography system, affinity chromatography system, supercriticalfluid chromatography system, ion exchange chromatography system,distillation system, fractional distillation system, thermal desorptionsystem, pseudo distillation apparatus, thermogravimetric analysisinstrument, or a pyrolysis instrument.
 17. A system as claimed in claim13, wherein the separator is a gas chromatography system.
 18. A systemas claimed in claim 13, wherein the current spectral responses and thepreviously acquired spectral responses are each averaged.
 19. A sampleanalysis system, comprising: a separator that provides components of asample over time; a spectrometry system that acquires spectral responsesof the components; and a computer system that compares current spectralresponses to a background that changes with time and comprisespreviously acquired spectral responses to identify and/or quantify newlygenerated components; wherein the computer system compares the currentspectral responses to spectral responses that were previously acquiredby an amount defined by skip time.
 20. A system as claimed in claim 19,wherein the skip time is between 20 seconds and 2 minutes.
 21. A systemas claimed in claim 19; wherein skip time is equal to or slightly longerthan the time required for a chromatographic peak to elute.
 22. A systemas claimed in claim 19, wherein the current spectral responses and thepreviously acquired spectral responses are absorbance spectra that werecalculated from averaged single beam sample spectra.
 23. A method foranalyzing a sample, comprising: generating components from a sample;acquiring spectral responses of the components over time; and comparingcurrent spectral responses to a background that changes with time andcomprises previously acquired spectral responses to identify and/orquantify newly generated components; wherein generating components fromthe sample comprises providing components that are not completelyseparated.
 24. A sample analysis system, comprising: a separator thatprovides components of a sample over time; a spectrometry system thatacquires spectral responses of the components; and a computer systemthat compares current spectral responses to a background that changeswith time and comprises previously acquired spectral responses toidentify and/or quantify newly generated components; wherein componentsprovided by the separator are not completely separated.